Abstract: The present invention relates to nucleotide sequences of the human Notch and Delta genes, and amino acid sequences of their encoded proteins, as well as fragments thereof containing an antigenic determinant or which are functionally active. The invention is also directed to fragments (termed herein "adhesive fragments"), and the sequences thereof, of the proteins ("toporythmic proteins") encoded by toporythmic genes which mediate homotypic or heterotypic binding to toporythmic proteins. Toporythmic genes, as used herein, refers to the genes Notch, Delta, and Serrate, as well as other members of the Delta/Serrate family which may be identified, e.g., by the methods described herein. Analogs and derivatives of the adhesive fragments which retain-binding activity are also provided. Antibodies to human Notch and to adhesive fragments are additionally provided.

Abstract: The present invention provides a cDNA of DOCK180 gene, which has a nucleotide sequence of SEQ ID No: 1 and of which translation product binds to the proto-oncogene product CRK, a recombinant vector containing this cDNA, a DOCK180 protein expressed from the cDNA which has a amino acid sequence of SEQ ID No: 2, and an antibody to the DOCK180 protein. According to the present invention, It is possible to develop new diagnosing and therapeutic techniques using DOCK180 protein and antibody against the protein.

Abstract: The present invention provides a cDNA of DOCK180 gene, which has a nucleotide sequence of SEQ ID NO: 1 and of which translation product binds to the proto-oncogene product CRK, a recombinant vector containing this cDNA, a DOCK180 protein expressed from the EDNA which has a amino acid sequence of SEQ ID NO: 2, and an antibody to the DOCK180 protein. According to the present invention, It is possible to develop new diagnosing and therapeutic techniques using DOCK180 protein and antibody against the protein.

Abstract: Aryl-substituted and aryl and (3-oxo-1-propenly)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity.

Abstract: The present invention features calcium receptor polypeptides and fragments thereof. Uses of a calcium receptor polypeptide include providing a polypeptide having the activity of a calcium receptor polypeptide. Calcium receptor polypeptide fragments can be used, for example, to generate antibodies to a calcium receptor polypeptide.

Abstract: The present invention relates to the discovery in mammalian cells, particularly human cells, of a novel CDK-binding protein, referred to herein as "cdc37". As described herein, this protein functions to facilitate activation and accordingly functions in the modulation of cell-cycle progression, and therefore ultimately of cell growth and differentiation. Moreover, binding data indicated that cdc37 may function coordinately with other cell-cycle regulatory proteins, such as of cyclin-dependent kinases (CDKs), src, p53 and erk kinases.

Abstract: The present invention relates to isolated MEKK proteins, nucleic acid molecules having sequences that encode such proteins, and antibodies raised against such proteins. The present invention also includes methods useful for identifying compounds capable of specifically regulating signal transduction in cells expressing MEKK protein.

Abstract: The present invention relates to amino acid sequences of the encoded deltex protein. The invention further relates to fragments and other derivatives, and analogs, of deltex proteins. In specific embodiments, the invention relates to deltex protein derivatives and analogs of the invention which are functionally active, or which comprise one or more domains of a deltex protein, including but not limited to the Gln-rich clusters, SH3 binding domains, domains which mediate binding to Notch or to a Notch derivative containing Notch cdc10/SW16/ankyrin ("ANK") repeats, domains which mediate binding to a second deltex protein, or any combination of the foregoing. The present invention also relates to compositions based on deltex proteins.

Abstract: The characterization of LXR.alpha., an orphan member of the nuclear hormone receptor superfamily that can function as a tissue-specific mediator of 9-cis retinoic acid (9cRA) is described herein. When expressed in cells, LXR.alpha. activates transcription in response to 9cRA on a distinct response element, termed an LXRE. Significantly, neither RXR homodimers nor RXR/RAR heterodimers are able to substitute for LXR.alpha. in mediating this retinoid response. The LXR.alpha. response to retinoids is due to its unique interaction with endogenous RXR. This interaction shifts RXR from its previously described role as a silent, heterodimer partner to an active ligand binding partner, thus defining a novel retinoid response pathway.

Abstract: A human brain glycoprotein homologous to the mouse F3 and the chicken contactin/F11 adhesion molecules, nucleic acid sequences encoding the human brain glycoprotein and antibodies directed against the human brain glycoprotein.

Abstract: Human hematopoietic stem cells are provided by separation of the stem cells from dedicated cells. The stem cells may than be maintained by regeneration in an appropriate growth medium. Means are provided for assaying for the stem cells as to their capability for producing members of each of the hematopoietic lineages.

Abstract: A method is described for screening retinoid X receptor agonists or antagonists using a retinoid X receptor expressed by a yeast expression system to screen a compound having a retinoid X receptor agonist or antagonist activity. Another screen is described for detecting a compound having retinoid X receptor agonist or antagonist activity by: (1) providing a yeast strain which expresses the retinoic acid receptor and activates a reporter plasmid containing apolipoprotein AI gene site A or a mutated variant thereof; (2) incubating the compound in suitable media and a colorless chromogenic substrate; and (3) examining the media for development of color. Mutated variants of apolipoprotein AI gene site A which respond selectively to the retinoid X receptor or respond to receptors other than RXR.alpha. are also described.

Abstract: A novel method for isolating novel secreted mammalian proteins is described in which mammalian secretory leader sequences are detected using the yeast invertase gene as a reporter system.

Abstract: A method is described for screening retinoid X receptor agonists or antagonists using a retinoid X receptor expressed by a yeast expression system to screen a compound having a retinoid X receptor agonist or antagonist activity. Another screen is described for detecting a compound having retinoid X receptor agonist or antagonist activity by: (1) providing a yeast strain which expresses the retinoic acid receptor and activates a reporter plasmid containing apolipoprotein AI gene site A or a mutated variant thereof; (2) incubating the compound in suitable media and a colorless chromogenic substrate; and (3) examining the media for development of color. Mutated variants of apolipoprotein AI gene site A which respond selectively to the retinoid X receptor or respond to receptors other than RXR.alpha. are also described.

Abstract: A method for activating a mammalian immune system entails a series of IL-2 administrations that are effected intermittently over an extended period. Each administration of IL-2 is sufficient to allow spontaneous DNA synthesis in peripheral blood or lymph node cells of the patient to increase and peak, and each subsequent administration follows the preceding administration in the series by a period of time that is sufficient to allow IL-2 receptor expression in peripheral or lymph node blood of the patient to increase, peak and then decrease to 50% of peak value. This intermittent IL-2 therapy can be combined with another therapy which targets a specific disease state, such as an anti-retroviral therapy comprising, for example, the administration of AZT, ddI or interferon alpha. In addition, IL-2 administration can be employed to facilitate in situ transduction of T cells in the context of gene therapy.

Abstract: Synthetic polypeptide analogs of parathyroid hormone PTH, parathyroid hormone related peptide PTHrp, and of the physiologically active truncated homologs and analogs of PTH and PTHrp, in which amino acid residues (22-31) form an amphipathic .alpha.-helix, these residues (22-31) selected from hydrophilic amino acids (Haa) and lipophilic amino acids (Laa) ordered in the sequence:Haa (Laa Laa Haa Haa).sub.2 Laaand their pharmaceutically acceptable salts are useful for the prophylaxis and treatment of ostoporosis in mammals. Processes for the production of the polypeptides via solid phase and recombinant methods are provided.

Abstract: The present invention relates to the discovery of novel proteins of mammalian origin which can associate with the human cyclin dependent kinase 4 (CDK4).

Abstract: The present invention relates to the different roles inorganic ion receptors have in cellular and body processes. The present invention features: (1) molecules which can modulate one or more inorganic ion receptor activities, preferably the molecule can mimic or block an effect of an extracellular ion on a cell having an inorganic ion receptor, more preferably the extracellular ion is Ca.sup.2+ and the effect is on a cell having a calcium receptor; (2) inorganic ion receptor proteins and fragments thereof, preferably calcium receptor proteins and fragments thereof; (3) nucleic acids encoding inorganic ion receptor proteins and fragments thereof, preferably calcium receptor proteins and fragments thereof; (4) antibodies and fragments thereof, targeted to inorganic ion receptor proteins, preferably calcium receptor protein; and (5) uses of such molecules, proteins, nucleic acids and antibodies.

Abstract: A human brain glycoprotein homologous to the mouse F3 and the chicken contactin/F11 adhesion molecules, nucleic acid sequences encoding the human brain glycoprotein and antibodies directed against the human brain glycoprotein.

Abstract: This invention describes a novel human brain Na.sup.+ -dependent inorganic phosphate cotransporter, designated the hBNPI protein. This invention also encompasses nucleic acids encoding this protein, or a fragment thereof, as well as methods employing this protein and the nucleic acid compounds.